HWA-152
Chemical Name: 3-Cyano-2,6-dimethyl-4-(4-thiomorpholinyl)pyridine N-oxide hydrochloride
CAS No. 106101-15-9, 106101-47-7 (free base)
项目整合开发状态: Clinical
项目研究机构: Cassella (Originator)
合成路线:The cyclization of ethyl acetoacetate (I) with 3-amino-2-butenenitrile (II) gives 4-hydroxy-2,6-dimethylpyridine-3-carbonitrile (III),which is treated with SOCl2 and oxidized with MCPBA to yield 4-chloro-2,6-dimethylpyridine-3-carbonitrile N-oxide (IV).Finally,this compound is condensed with thiomorpholine (V) to afford the target compound.
📌 参考资料/链接：
参考文献标题:Substd.pyridin-1-oxides,process for their preparation,medicines containing them and their use
文献作者:Greve,W.; Schindler,U.; Elben,U.; Rudolphi,K.(Aventis Pharma AG)
参考来源:DE 3514073
📄 详细内容
合成路线:The cyclization of ethyl acetoacetate (I) with 3-amino-2-butenenitrile (II) gives 4-hydroxy-2,6-dimethylpyridine-3-carbonitrile (III),which is treated with SOCl2 and oxidized with MCPBA to yield 4-chloro-2,6-dimethylpyridine-3-carbonitrile N-oxide (IV).Finally,this compound is condensed with thiomorpholine (V) to afford the target compound.
参考文献标题:4-Hydroxy-2,6-dimethylnicotinic acid esters
文献作者:Nemcova,D.; Janata,V.
参考来源:CS 147252
合成路线:The cyclization of ethyl acetoacetate (I) with 3-amino-2-butenenitrile (II) gives 4-hydroxy-2,6-dimethylpyridine-3-carbonitrile (III),which is treated with SOCl2 and oxidized with MCPBA to yield 4-chloro-2,6-dimethylpyridine-3-carbonitrile N-oxide (IV).Finally,this compound is condensed with thiomorpholine (V) to afford the target compound.
合成路线:The reaction of 3-acetyl-6-methyl-3,4-dihydro-2H-pyran-2,4-dione (I) with ammonia gives 2,6-dimethylpyridin-4-ol (II),which is nitrated with HNO3/H2SO4 and treated with SOCl2 to yield 4-chloro-2,6-dimethyl-3-nitropyridine (III).The condensation of (III) with ethanolamine (IV) affords N-(2,6-dimethyl-3-nitropyridin-4-yl)ethanolamine (V),which is finally condensed with 1-(diphenylmethyl)piperazine (VI) by means of SOCl2 and treated with HCl to furnish the target trihydrochloride.
参考文献标题:SUBSTITUTED DIALKYLPYRIDINES AND THEIR N-OXIDES WITH AN ELECTRON-WITHDRAWING SUBSTITUENT
文献作者:Elben,U.
参考来源:Drugs Fut 1989,14(10),981